Carrier-Free Rapamycin-Loaded Nanoparticles with MRI and Near-Infrared Fluorescence Bimodal Imaging for Precise Diagnosis and Synergistic Therapy of Ischemic Stroke

Background Ischemic stroke (IS) management is challenged by low drug delivery efficiency and limitations in current imaging modalities. We aimed to assemble rapamycin (RAPA), indocyanine green (ICG), epigallocatechin-3-gallate (EGCG), and Gd3+ as neuroprotective drugs, near-infrared fluorescence (NIRF) imaging agents, biomimetic coatings, and MRI agents, respectively, into a carrier-free, dual-modal imaging-guided theranostic nanoplatform (IREGd NPs) for the integrated diagnosis and therapy of IS.Methods The physicochemical properties, cytotoxicity, drug release characteristics, and cellular uptake of IREGd NPs were characterized. Therapeutic efficacy was evaluated in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) models of cell injury and in vivo in a transient middle cerebral artery occlusion (tMCAO) rat model. Outcomes included sensorimotor function, cerebral infarct volume, brain edema, neuronal apoptosis, neuroinflammation, oxidative stress, and biodistribution. The bimodal imaging properties were verified in vitro and in vivo.Results IREGd NPs demonstrated good dispersibility and stability, with a RAPA loading efficiency of 65.9 wt%, enabling enhanced MRI and NIRF imaging capabilities with a longitudinal relaxation rate of 40.18 mM−1·s−1 for precise visualization of the ischemic region and drug biodistribution. In vitro experiments confirmed effective cellular uptake and superior neuroprotective effects in OGD/R-treated cells compared with RAPA or EGCG alone. Finally, in vivo experiments in rats with tMCAO confirmed that IREGd NPs passively accumulated in the ischemic hemisphere, enabling accurate bimodal imaging and exerting neuroprotective effects, as evidenced by improved sensorimotor function, reduced cerebral infarct volume and brain edema, decreased neuronal apoptosis, and attenuated neuroinflammation and oxidative stress, outperforming individual RAPA or EGCG treatment. Histology revealed no systemic toxicity.Conclusion IREGd NPs efficiently deliver RAPA, and the neuroprotective effects are exerted by RAPA in combination with EGCG. Dual-modal imaging enables precise visualization of the ischemic region and drug biodistribution. These results suggest the translational potential of the biomimetic nanotheranostic platform for the treatment of IS.